Description: (Applicant's Description) A hallmark of tumor cells is their capacity for unlimited replication, or cellular immortality. The ribonucleoprotein enzyme telomerase, which is necessary for cell immortality, is a target in cancer cells that can be exploited for the discovery of new therapeutic modalities. Current anti-cancer therapeutics attempt to contain this growth potential either through reducing the tumor burden (e.g., with surgery, cytotoxic/cytostatic agents, or radiation) or by manipulating the environment of the tumor to limit growth. In contrast to most oncolytic drugs, telomerase inhibitors should exhibit a large therapeutic index since cancer cells do express telomerase and most normal cells do not. The objective of the Compound Evaluation Group is to discover and develop lead compounds as telomerase inhibitors. A telomerase drug discovery program has been established which has already generated three lead series that are under active investigation. New chemical entities are first evaluated for telomerase inhibition in a high throughput cell-free. Active compounds will be profiled in secondary assays to establish their mechanism of action and specificity. Successive iterations of chemical modifications followed by compound evaluation in the secondary assays will be used to improve the potency and specificity of promising compound(s). When sufficient potency and specificity are achieved, the compound will be tested in ex viva and in viva tumor models.